TY - JOUR
T1 - Efficacy and safety of abatacept in active primary Sjögren's syndrome
T2 - Results of a phase III, randomised, placebo-controlled trial
AU - Baer, Alan N.
AU - Gottenberg, Jacques Eric
AU - St Clair, E. William
AU - Sumida, Takayuki
AU - Takeuchi, Tsutomu
AU - Seror, Raphaèle
AU - Foulks, Gary
AU - Nys, Marleen
AU - Mukherjee, Sumanta
AU - Wong, Robert
AU - Ray, Neelanjana
AU - Bootsma, Hendrika
N1 - Funding Information:
3Department of Medicine, Duke University Medical Center, Durham, North Carolina, USA 4Department of Internal Medicine, University of Tsukuba, Tsukuba, Ibaraki, Japan 5Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan 6Department of Rheumatology and National Reference Center for Sjögren Syndrome and Rare Autoimmune Diseases, AP-HP Université Paris-Saclay, INSERM UMR1184, Le Kremlin Bicêtre, Paris, France 7Department of Ophthalmology and Visual Sciences, University of Louisville School of Medicine, Louisville, Kentucky, USA 8Global Biometric Sciences, Bristol Myers Squibb, Braine L’Alleud, Belgium 9Innovative Medicines and Development – Clinical Biomarkers, Bristol Myers Squibb Company, Princeton, New Jersey, USA 10Immunology and Fibrosis, Bristol Myers Squibb Company, Princeton, New Jersey, USA 11Global Drug Development – Immunology, Bristol Myers Squibb Company, Princeton, New Jersey, USA 12Department of Rheumatology and Clinical Immunology, University of Groningen, University Medical Center Groningen, Groningen, Netherlands Acknowledgements These data were presented in part at EULAR 2019 (OP0039) and ACR 2019 (1907). We thank the patients and all the investigators who participated in the study. We thank the contributions of Marianne Peluso as protocol manager of this study. Professional medical writing and editorial assistance was provided by Fiona Boswell, PhD, at Caudex, and was funded by Bristol Myers Squibb Company.
Funding Information:
This study was sponsored by Bristol Myers Squibb Company.
Publisher Copyright:
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PY - 2021/3/1
Y1 - 2021/3/1
N2 - Objectives To evaluate efficacy and safety of abatacept in adults with active primary Sjögren's syndrome (pSS) in a phase III, randomised, double-blind, placebo-controlled trial. Methods Eligible patients (moderate-to-severe pSS [2016 ACR/European League Against Rheumatism (EULAR) criteria], EULAR Sjögren's Syndrome Disease Activity Index [ESSDAI] ≥5, anti-SS-related antigen A/anti-Ro antibody positive) received weekly subcutaneous abatacept 125 mg or placebo for 169 days followed by an open-label extension to day 365. Primary endpoint was mean change from baseline in ESSDAI at day 169. Key secondary endpoints were mean change from baseline in EULAR Sjögren's Syndrome Patient Reported Index (ESSPRI) and stimulated whole salivary flow (SWSF) at day 169. Other secondary clinical endpoints included glandular functions and patient-reported outcomes. Selected biomarkers and immune cell phenotypes were examined. Safety was monitored. Results Of 187 patients randomised, 168 completed double-blind period and 165 continued into open-label period. Mean (SD) baseline ESSDAI and ESSPRI total scores were 9.4 (4.3) and 6.5 (2.0), respectively. Statistical significance was not reached for primary (ESSDAI -3.2 abatacept vs -3.7 placebo, p=0.442) or key secondary endpoints (ESSPRI, p=0.337; SWSF, p=0.584). No clinical benefit of abatacept over placebo at day 169 was seen with other clinical and PRO endpoints. Relative to baseline, abatacept was associated with significant differences vs placebo in some disease-relevant biomarkers (including IgG, IgA, IgM-rheumatoid factor) and pathogenic cell subpopulations (post hoc analyses). No new safety signals were identified. Conclusions Abatacept treatment did not result in significant clinical efficacy compared with placebo in patients with moderate-to-severe pSS, despite evidence of biological activity.
AB - Objectives To evaluate efficacy and safety of abatacept in adults with active primary Sjögren's syndrome (pSS) in a phase III, randomised, double-blind, placebo-controlled trial. Methods Eligible patients (moderate-to-severe pSS [2016 ACR/European League Against Rheumatism (EULAR) criteria], EULAR Sjögren's Syndrome Disease Activity Index [ESSDAI] ≥5, anti-SS-related antigen A/anti-Ro antibody positive) received weekly subcutaneous abatacept 125 mg or placebo for 169 days followed by an open-label extension to day 365. Primary endpoint was mean change from baseline in ESSDAI at day 169. Key secondary endpoints were mean change from baseline in EULAR Sjögren's Syndrome Patient Reported Index (ESSPRI) and stimulated whole salivary flow (SWSF) at day 169. Other secondary clinical endpoints included glandular functions and patient-reported outcomes. Selected biomarkers and immune cell phenotypes were examined. Safety was monitored. Results Of 187 patients randomised, 168 completed double-blind period and 165 continued into open-label period. Mean (SD) baseline ESSDAI and ESSPRI total scores were 9.4 (4.3) and 6.5 (2.0), respectively. Statistical significance was not reached for primary (ESSDAI -3.2 abatacept vs -3.7 placebo, p=0.442) or key secondary endpoints (ESSPRI, p=0.337; SWSF, p=0.584). No clinical benefit of abatacept over placebo at day 169 was seen with other clinical and PRO endpoints. Relative to baseline, abatacept was associated with significant differences vs placebo in some disease-relevant biomarkers (including IgG, IgA, IgM-rheumatoid factor) and pathogenic cell subpopulations (post hoc analyses). No new safety signals were identified. Conclusions Abatacept treatment did not result in significant clinical efficacy compared with placebo in patients with moderate-to-severe pSS, despite evidence of biological activity.
KW - Sjogren's syndrome
KW - autoimmune diseases
KW - therapeutics
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U2 - 10.1136/annrheumdis-2020-218599
DO - 10.1136/annrheumdis-2020-218599
M3 - Article
C2 - 33168545
AN - SCOPUS:85096075489
VL - 80
SP - 339
EP - 348
JO - Annals of the Rheumatic Diseases
JF - Annals of the Rheumatic Diseases
SN - 0003-4967
IS - 3
ER -